Bernard Vanabelle

Options for fertility preservation in prepubertal boys

BACKGROUND Fertility in adult life may be severely impaired by gonadotoxic therapies. For young boys who do not yet produce spermatozoa, cryopreservation of immature testicular tissue (ITT) is an option to preserve their fertility, albeit still experimental. This paper covers current options for ITT cryopreservation and fertility restoration. METHODS Relevant studies were identified by an extensive Medline search of English and French language articles. Search terms were: gonadotoxicity, cytoprotection, cryopreservation, ITT, spermatogonia, testicular transplantation, testicular grafting and in vitro maturation (IVM). RESULTS Although no effective gonadoprotective drug is yet available for in vivo spermatogonial stem cell protection in humans, current evidence supports the feasibility of ITT cryopreservation before gonadotoxic treatment with a view to fertility preservation. Controlled slow freezing with dimethyl sulfoxide allows survival and proliferation of human spermatogonia after xenotransplantation, but only partial differentiation. Animal data look promising, since healthy offspring have been obtained after transplantation of frozen testicular cell suspensions or tissue pieces. However, none of the fertility restoration options from frozen tissue, i.e. cell suspension transplantation, tissue grafting and IVM have proved efficient and safe in humans as yet. CONCLUSION While additional evidence is required to define optimal conditions for ITT cryopreservation with a view to transplantation or IVM, the putative indications for such techniques, as well as their limitations according to disease, are outlined.

Bone marrow transplantation or hydroxyurea for sickle cell anemia: long-term effects on semen variables and hormone profiles.

Ten male subjects affected by sickle cell anemia (SCA) were studied to evaluate the long-term effects of therapies on their fertility. Their ages ranged from 18 to 34 years (median: 32 years). Four subjects were treated by hydroxyurea (HU) and 6 by hematopoietic stem cell transplantation (HSCT). The median follow-up after HU initiation and HSCT was 10.5 years (range: 8–15 years) and 15.5 years (range: 8–21 years), respectively. Three of the 6 in the HSCT group and two of the 4 in the HU group were azoospermic. One HSCT subject had normal semen and hormone variables, showing that normal fertility can occasionally be expected after transplantation in SCA. The remaining 4 patients (2 HSCT and 2 HU) were oligozoospermic. With regard to HU, semen impairment appears to be related to the duration of treatment. To draw general conclusions, further research with a large number of patients treated since childhood with HU or HSCT is warranted.